Variant 6-31642909-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001387994.1(BAG6):c.1963T>C(p.Ser655Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,609,852 control chromosomes in the GnomAD database, including 192,892 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 16025 hom., cov: 32)

Exomes 𝑓: 0.49 ( 176867 hom. )

Consequence

BAG6
NM_001387994.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.560

Variant links:

Genes affected

BAG6 (HGNC:13919): (BAG cochaperone 6) This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

BAG6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.3527514E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAG6	NM_001387994.1 linkuse as main transcript	c.1963T>C	p.Ser655Pro	missense_variant	15/26	ENST00000676615.2	NP_001374923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAG6	ENST00000676615.2 linkuse as main transcript	c.1963T>C	p.Ser655Pro	missense_variant	15/26		NM_001387994.1	ENSP00000502941	A2	P46379-3

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68381

AN:

151860

Hom.:

16006

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.616

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.375

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.486

Gnomad OTH

AF:

0.482

GnomAD3 exomes

AF:

0.507

AC:

123046

AN:

242662

Hom.:

31996

AF XY:

0.517

AC XY:

67933

AN XY:

131468

show subpopulations

Gnomad AFR exome

AF:

0.331

Gnomad AMR exome

AF:

0.509

Gnomad ASJ exome

AF:

0.625

Gnomad EAS exome

AF:

0.596

Gnomad SAS exome

AF:

0.596

Gnomad FIN exome

AF:

0.386

Gnomad NFE exome

AF:

0.503

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.489

AC:

713223

AN:

1457874

Hom.:

176867

Cov.:

AF XY:

0.495

AC XY:

358718

AN XY:

724972

show subpopulations

Gnomad4 AFR exome

AF:

0.333

Gnomad4 AMR exome

AF:

0.509

Gnomad4 ASJ exome

AF:

0.614

Gnomad4 EAS exome

AF:

0.582

Gnomad4 SAS exome

AF:

0.590

Gnomad4 FIN exome

AF:

0.382

Gnomad4 NFE exome

AF:

0.484

Gnomad4 OTH exome

AF:

0.493

GnomAD4 genome

AF:

0.450

AC:

68444

AN:

151978

Hom.:

16025

Cov.:

AF XY:

0.450

AC XY:

33425

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.338

Gnomad4 AMR

AF:

0.499

Gnomad4 ASJ

AF:

0.616

Gnomad4 EAS

AF:

0.607

Gnomad4 SAS

AF:

0.588

Gnomad4 FIN

AF:

0.375

Gnomad4 NFE

AF:

0.486

Gnomad4 OTH

AF:

0.485

Alfa

AF:

0.497

Hom.:

38093

Bravo

AF:

0.452

TwinsUK

AF:

0.491

AC:

1821

ALSPAC

AF:

0.489

AC:

1886

ESP6500AA

AF:

0.338

AC:

1491

ESP6500EA

AF:

0.487

AC:

4184

ExAC

AF:

0.499

AC:

60495

Asia WGS

AF:

0.598

AC:

2082

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.31

DEOGEN2

Benign

0.065

.;.;T;.;.;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.25

MetaRNN

Benign

0.000054

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

.;.;N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

0.46

N;N;N;N;N;N

REVEL

Benign

0.080

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

0.54

T;T;T;T;.;T

Polyphen

0.0

B;B;B;.;.;.

Vest4

0.049

MPC

0.51

ClinPred

0.0053

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over